The Cancer Genome Characterization Center (CGCC) at the Broad Institute of MIT and Harvard brings together a team of investigators with extensive expertise in cancer and genomics, as well as a track record of setting and attaining milestones. As part of The Cancer Genome Atlas (TCGA) pilot project, we propose to accomplish the following objectives: (1) Characterize structural alterations (amplification, deletion and LOH) and gene expression in a large collection of cancer samples. Specifically, we will use microarrays to perform high-density SNP genotyping and RNA expression profiling. We will analyze 1000, 1500 and 2000 samples in years 1, 2 and 3, respectively - with costs decreasing to allow an increasing number of samples on a roughly constant budget. (2) Improve the cost and performance of SNP genotyping and RNA expression profiling, by designing new, more efficient arrays. In particular, we will decrease total costs by a factor of at least 2-fold for the same information content. By the end of the project, it will be possible to characterize genome alteration and gene expression in a collection of 15,000 cancer samples (the target suggested in NCI's report on TCGA) at a total cost of <$6M/year over a three-year period. These technologies will thus be ready for full scale up within TCGA. (3) Cross-validate, integrate, and analyze CGCC data to determine regions of genome alteration for high-throughput sequencing. (4) Rapidly share data with the cancer research community. [unreadable] [unreadable] [unreadable] [unreadable]